Feed efficiency promoting composition



United States Patent a 2,927,021 .FEED EFFICIENCY PROMOTING COMPOSITION No Drawing. Application November 20, 1957,

Serial No.697,541

3 Claims. I (Cl. 99- -2 This invention relates to animal feed efficiency promotirlg compositions and methods employing as an essential active ingredient one or more compounds from the group including the salts, esters, amides, and cyclic monolactones and dilactones of4,5-dihydroxy-2,4,6-octatrienedioic acid and its derivatives.

Substances which efiectively stimulate the growth rate and increase the feed efiiciency of animals have great value,particularly to the agricultural economy. Such substances can shorten the time normally necessary to rear animals for marketing by accelerating the rate of weight gained. They also can lower the cost of raising animals by improving feed efliciencies. It has been found that the growth rate and in particular the efiiciency of feed utilization of animals can be markedly increased by the active ingredients of the present invention more particularly described below.

Animals whose feed efliciency can be promoted by the active ingredients of the present invention include livestock such as goats, mules, donkeys, horses, sheep, cattle, and swine, poultry such as ducks, chickens, geese and turkeys, household pets such as dogs and cats, experimental laboratory animals such as rats, monkeys, mice, guinea pigs and rabbits, commercially valuable animals such as mink, chinchillas and foxes as well as other domesticated and wild animals, including squirrels, skunks, beavers, etc.

The essential active ingredients necessary for the feed efliciency promoting compositions and methods of this invention are the salts, esters, amides, and cyclic lactones of 4,5-dihydroxy-2,4,6-octatrienedioic acid and its derivatives. These essential active ingredients include compounds represented by the formula:

( r Yr 0 5 5 0 X1: a-C=oa=c -c=o-i 3-X2 it is R R wherein: R and R can be the same or different and are selected from the group consisting of hydrogen; alkoxyaryl, especially where the alkoxy radical is not more than 12 carbon atoms and the aryl radical is hydrocarbon of not more than carbon atoms; haloaryl, especially chloroaryl where the aryl radical is hydrocarbon of not more than 10 carbon atoms; and monovalent hydrocarbon radicals free from non-aromatic unsaturation, especially of not more than 12 carbon atoms, e.g., alkyl apecially short chain alkyl, i.e. containing less than 7 carbon atoms, aryl especially where the aryl radical is hydrocarbon of not more than 10 carbon atoms, and aralkyl especially of not morethan 7 carbon atoms; X and X; can be the same or different and are selected from the group consisting of 1 wherein R and R can be the same or different and are selected from the group consisting of hydrogen, monovalent hydrocarbon radicals free from non-aromatic unsaturation especially of not more than 18 carbon atoms such as, for example, alkyl and especially short chain alkyls containing less than 7 carbon atoms, haloalkyl, aralkyl, alkoxyl, aryl, haloaryl especially chloroaryl where the aryl radical is hydrocarbon of not more than 10 carbon atoms, and alkoxyaryl especially where the alkoxy radical is not more than 12 carbon atoms and the arylradical is hydrocarbon of not more than 10 carbon atoms; 0R wherein R is from the group consisting of hydrogen, monovalent hydrocarbon radicals free from non-aromatic unsaturation especially of not more than 12 carbon atoms such as, for example, alkyl and especially short chain alkyls containing less than 7 carbon atoms, haloalkyl, aralkyl, alkoxyl, aryl, haloaryl especially chloroaryl where the aryl radical is hydrocarbon of not more than 10 carbon atoms and alkoxyarylespecially where the alkoxy radical is not morethan 12 carbon atoms and the aryl radical is hydrocarbon of not more than 10 carbon atoms, provided that only one of the X and X radicals can be OH in a single compound; and OM wherein M is a cation such as, for example, sodium, potassium, calcium, ammonium, quaternary ammonium, aluminum, nickelic, cobaltic, ferric, manganic, and cupric; and Y and Y can be the same or different and are selected from the group consisting of hydrogen and alkali metal, and monocyclic anddicyclic derivatives being represented by Formula 1 wherein X, and Y or X and Y are removed to form the corresponding monolactone, or'both of these combinations are removed to form the corresponding dilactone. Of the above compounds and cyclic derivatives, the di-gamma-lactone has particular advantages.

The compounds of the class est forth above have been only recently discovered. The compounds and methods for their preparation are described and claimed in U.S. applications, Serial Numbers 549,154 and 549,155, both filed November 25, 1955, said Serial Number 549,155 now U.S. Patent Number 2,840,570.

The unsaturated dilactones having thestructure described above and in which R and R are H are characterized in having specific absorption coefficients in the neighborhood of 3300 to 3400 angstroms of 200 to 224, melting points from 220 to 250. C., and havinga hydro-. gen number, determined with palladium-on-charcoal, corresponding to about 3 moles of hydrogen per molecule. These dilactones can be prepared by reacting acetylene and carbon monoxide in an inert organic solvent in contact with a cobalt carbonyl catalyst. In one method of preparation, a pressure reactor is charged with an inert organic solvent, i.e., one free from active hydro gen. A catalytic amount of a cobalt carbonyl catalyst is added, the reactor is closed, cooled to 0 C., or lower, and evacuated. A predetermined amount of acetylene is then admitted from a storage vessel calibrated so that the amount of acetylene, delivered is measured by the drop in pressure, and the reactor placed in a shaking device. Carbon monoxide is introduced to between 50 and 3000 atmospheres, usually 250 to 1000 atmospheres, and

the charge heated and agitated at 60 to (3., usually After reaction is complete, the reactor is permitted to a cool, unreacted acetylene and carbon monoxide are vented to the atmosphere, and the reaction mixtureslurried with an inert organic solvent. The slurry is filtered and Patented Mar. 1, 1960,

solvent. The extract is cooled and the crystalline prodnot which separates is filtered and dried. An alternative method for isolating the desired dilactone is by heating the crude reaction product at 200 C. and 1-2 mm. pressure, and collecting the sublimate on a cold finger.

In the formation of the dilactones, there are involved two moles of an acetylene and 4 moles of carbon monoxide. In practice, this ratio is attained by charging a weighed sample of the acetylene into the reactor and then injecting carbon monoxide in an amount sutficient to provide 2 moles thereof per mole of acetylene. Employing a 400 milliliter reactor and 25-30 grams of acetylene, the amount of carbon monoxide injected is that which will provide a total pressure in the range of 50-3000 atmospheres at reaction temperature. The reaction generally requires from 1 to 20 hours, although shorter or longer reaction times can be employed.

The reaction between the acetylene and carbon monoxide can be carried out batchwise or continuously in the presence of an inera organic liquid medium. By inert organic liquid medium is meant organic liquids which contain no active hydrogen, as determined by the Zerewitinoff method [Ber. 40, 2926 (1927); J. Am. Chem. Soc. 49, 3181 (1827)]. Thus, the acetylene is the only compound in the reaction system which may contain active hydrogen. Specific inert organic liquids are isooctane, toluene, acetonitrile, acetone, cyclohexanone, ethyl acetate, dioxane, diethyl ether, xylene, benzene, etc. The nitriles and ketones are in general preferred over the hydrocarbons and ethers.

The amount of solventused can be varied over wide limits but generally it is at least equal to the Weight of the acetylene charged into the reactor. An amount in excess of ten times the weight of the acetylene is commonly advantageous from the standpoint of yield, and even 20 or more times is sometimes preferred.

The catalysts used are the cobalt carbonyls and the compounds formed by reaction of cobalt carbonyl with electron donor solvents such as ketones and nitriles that fall within the definition of inert organic media given above. Cobalt acetylacetonate can be used as an equivalent for cobalt carbonyl. Cobalt carbonyl can be made by direct reaction of carbon monoxide with the metal in reactive form, as described in I. Am. Chem. Soc. 70, 383-6 '(1948). The amount of catalyst employed is generally from 0.01 to 1 5% based on the acetylene charged into the reactor.

The dilactones' suitable according to the present invention furthermore can exist in isomeric forms. Among the isomeric forms of the unsaturated dilactones can be mentioned the cis and trans forms of [h -bifuran]-5,5'-dione, as follows:

The lower melting isomer has a melting point of230- 237 C. and the higher melting isomer has a melting point of 240248 (3., determined in a capillary tube in an electrically heated melting point apparatus. The isomers can be recrystallized repeatedly from methyl ethyl 'ketone to give samples melting at 235 and 247 C.,

respectively, when a setting is used such that the temperature increases from 17 to 200 ,C. in 6 minutes, from 200 to 225 C. in '9 minutes, and from 225 to 247 C. in 11 minutes. The melting is generally accompanied by sublimation and decomposition.

The two isomers are further distinguished by their ultraviolet absorption; the pure lower melting isomer has its maximum absorption at about 34.00 A. and its specific absorbance, k A, is 2QO-20-4. The pure higher melting isomer has its maximum absorption at about 3350 A. and its specific absorbance k is 220 224.

The low melting isomer can be isomerized to the high melting or cis form by treating it with sulfuric or phosphoric acid or pyridine. The cis isomer can also be obtained from the trans isomer by recrystallization of the trans isomer from dimethylformamide. It can also be produced directly from carbon monoxide and acetylene by including hydrogen sulfide or a strong acid in the re action mixture.

The alkali metal salts of 4,5-dihydroxy-2,4,6'-octatrienedioic acid esters, having a structure of Formula 1 wherein X and X are 011;; and wherein Y and Y are alkali metal, are formed when a dilactone, prepared for example as described above, is treated with an alkali metal alkoxide in alcoholic mediunr A monolactone monoester having the structure of Formula 1' can be obtained by acidifying the alkali metal salts of the diesters referred to in the preceding paragraph. The other monolactone compounds having a structure of Formula 1 can be prepared by subjecting a dilactone of the type described above to reaction with the basic reagent and then acidifying the resulting reaction mixture. When the basic reagent is an aqueousalkali metal hydroxide, there is obtained, on acidification, the

monolactone acid.- When the basic reagent is alcoholic alkali metal alkoxide, there is obtained on acidification a monolactone monoester. When the basic reagent is ammonium hydroxide, or a primary or secondary monoamine, there is obtained on acidification a monolactone monoamide. The monolactone acid salts, the monolactone monoesters, and the monolactone monoamides are hydrolyzable to the corresponding monolactone acids.

The monolactone monoamides and the monoiactone monoestcrs of Formula 1 are shown by infrared data to be gamma-monolactones, while the monolactoue acids are shown to be delta-monolactones.

In the preparation of the monolactone compounds referred to above, the basic reagent is not especially critical and can include such usefully employable hydrolytic agents as ammonium, sodium, potassium, and lithium hy droxides, monoand dibutylamines, monoand vdicotyl-v amines, N-methylaniline, N-octylamine, N-cyclohexylaniline, benzylamine, N-methylbenzylamine, cyclohexylamine, N-cyclohexylaniline, toluidi nes, xylylamines, so-i dium ethoxide, potassium butoxide, sodium dodecyloxide, aminotoluic acids, dimethylamine, octadecylaminc, p1 anisidine, piperidine, morpholine, and other monoamines having hydrogen attached to amino nitrogen with the amino group as the sole functional group reactive toward carboxyl.

The hydrolysis of the dilactone can be effected at tern peratures 'varying from normal room temperature to reflux at atmosphere pressure. The hydrolytic agent and dilactone are used in at least 1:1 molaramounts. In practice, however, it is preferred to use amounts of the hydrolytic agent which are several times the molar amount ofthe dilactone present in the reaction mixture. The hydrolysis is usually effected in the presence of a reaction medium and suitable media include water, alcohols, such as methanol, ethanol, etc.; ethers, such as dioxane; hydrocarbons, such as benzene, toluene, xylene, isooctane, and the like.

The'strength of the acid used in acidifying the reaction mixture after hydrolysis withaqueous alkali metal or alkaline earth metal hydroxide determines the nature of the product obtained. Thus, with hydrochloric acid,..thc product can be the rnonosodium salt of the monolactoue acid, while with acetic acid it is the monosodiurn salt of the open chain acid. a a

The amount of reaction medium is not critical but for convenience of operation an amount is usually employed which exceeds the combined weight of the reactants by several fold. The reaction medium can be a solvent for the dilactohc andhydrolytic reactant or it can be a solvent for one and not for the other.

The examples given: below illustrate methods of synthesis of compounds involved in the present invention and serve to exemplify for those having ordinary skill in the art techniques for the preparation of the active ingredicuts of the present invention. l

i Extzmple A 1 A 400 milliliter stainless steel shaker tube is flushed with nitrogen and charged with 100 milliliters of acetonitrile' containing one gram of cobaltcarbonyl; The tube is closed, cooled in solid carbon dioxide/methanol, and nitrogen is removed by evacuation. By means of a calibrated reservoir, 26 grams of acetylene, previously passed through two towers containing activated alumina and sodium hydroxide, is added to the shaker tube. The shaker tube is placed in an electrically heated box which is shaken vigorously. Carbon monoxide in introduced into the shaker tube, as the tube is warmed up, and the actual reaction is carried out at 110 C. during 15 hours at a pressure varying from 700 to 900 atmospheres.

Carbon monoxide is added periodically as required to maintain this pressure. The carbon monoxide absorptionzis quite brisk, especially during the early stages of the run. A duplicate run is made and the two runs composited for work up. The reaction mixture is slurried with ether and filtered. The moist precipitate weighs 130.5 grams/The precipitate is extracted with hot acetonitrile and this extract upon cooling on ice deposits 13 grams of brick red crystals, melting at 220 C. After recrystallization from ethyl acetate, the product has "an ultraviolet absorption maximum in acetonitrile of 3400 angstroms. The compound is the dilactone [A 'Q bituran]-5,5'-dione and shows a strong absorption in the infrared at 5.65 microns for lactone carbonyl unsaturationand a single very strong band at 6.50 microns due to C=C unsaturation.

Example B A solution in 200 ml. of concentrated ammonium hydroxide of 15.5 grams of the dilactone prepared as in EX- arnple A is prepared by stirring with gentle warming for a few minutes. The orange-brown solution is filtered and acidified with concentrated hydrochloric acid with external cooling, The yellow precipitate weighs 4.0 grams when dry and is soluble in dilute aqueous sodium hydroxide. The product is the gamma-monolactone monoamide of 4,5-dihydroxy-2,4,6-octatrienedioic acid.

Example Cv To 60grams of the unsaturated dilactone prepared as in Example A is added 450 milliliters of aqueous sodium hydroxide and the mixture warmed until solution results. The solution is then filtered to remove 3.2 grams of unchanged dilactone. The filtrate is poured into a solution of 100 milliliters of acetic acid in 900 milliliters of water. After scratching the Walls of the container with aglass rod, there separates 46.7 grams"(6l%) of a yellow-orange solid. This product is the monosodium salt of the open chain acid, 4,5-dihydroxy-2,4,fi-octatrienedioic a cid. i

Example E Metal salts are precipitated from aqueous solutions of the monosodium salt prepared as in Example D by addition of the proper cation. Suitable exemplary salts Salt Added Color of Product Ni(NO3)2 Yellow. Oo(0Ac) Yellow-Orange. MnSOi Yellow. Al(OAa)3 D0.

F8013-.. Dark Brown.

Gl1(OAc) Pale Green. Ba(OH)z Yellow.

Example F A solution is prepared by stirring together 15.3 grams (0.093 mole) of a dilactone prepared as in Example A, and a solution of 5.2 grams (0.096 mole) of sodium.

methoxide in 200 milliliters of methanol. To this mixture glacial acetic acid (6 milliliters) is added and the yellow precipitate (15.7 grams) collected and dried..

By chilling the filtrate, another 1.1 grams'is obtained.

The total yield is 16.8 grams (92%). The compound. is sparingly soluble in water and does not react with. dilute sodium bicarbonate solution. The compound can. be readily purified by recrystallization from methanol.

or methyl ethyl ketone and is the gamma-monolactone monomethyl ester acid.

Illustrative of the salts, esters, amides, and cyclic: monolactones and dilactones of 4,5-dihydroxy-2,4,6-octa-- trienedioic acid and its derivatives employedin the growth:

promoting compositions and methods of the invention:

are the following:

4,5-dihydroxy-2,4,6-octatrienedioic acid, monosodium:

salt 4,5-dihydroxy-2,4,6-octatrienedioic acid, ammonium salt M 4,5-dihydroxy-2,4,6-octatrienedioic acid disodium salt 4,5-dihydroxy-cis-2,cis-4,cis-6-octatrienedioic acid, di-- gamma-lactone 4,5-dihydroxy-cis-2,trans-4,cis-6-octatrienedioic acid, di-- gamma-lactone l 1 2,6 bis (p-chlorophenyl)-4,5-dihydroxy-cis-;2,trans-4,cis-6 octatrienecli oic acid, di-gamma-lactone 3,7 bis(p-chloropheny1) -4,5-dihydroxy-cis-i2,trans-4,cis-6 octatrienedioic acid, di-garnma-lactone l 4,5-dihydr0xy-2,6-di-2-naphthylcis-2,trans-4,cis 6 octatrienedioic acid, di-gamma-lactone 4,5 dihydroxy-3,7-di-2-naphthyl-cis-2,trans-4,cis 6 octa-v trienedioic acid, di-gamma-lactone 4,5 dihydroxy-2,6-diphenyl-cis-2,trans-4,cis-6-octatriene dioic acid, di-gamma-lactone 5 4,5 dihydroxy-3,7-diphenyl-cis-2,trans-4,cis-6 octatriene dioic acid, di-gamma-lactone 2,6-bis(o-methoxyphenyl) -4,5-dihydroxy-cis-2,trans-4,cis

6-octatrienedi0ic acid, di-gamma-lactone 3,7-fbis (o-methoxyphenyl) -4,5-dihydroxycis-2,trans-4,cis 6-octatrienedioic acid, di-gamma-lactone 2,6-dibutyl-4,5-dihydroxy-cis-2,trans-4,cis 6 octatriene dioic acid, di-gamma-lactone 3,7-dibutyl-4,5-dihydroxy-cis-2,trans 4,cis 6 octatriene dioic acid, di-gamma-lactone j 4,5 dihydroxy 2,6-dimethyl-cis-2,trans-4,cis-6-octatriencdioic acid, di-gamma-lactone I of 4,5-dihydroxy-2,4,d-octatrienedioic:

seams? 4,5 dihydroxy-3,7-dimethyl-cis-2,trans-4,cis-6-octatrienedioic acid, di-gamma-lactone (p-Carboxyphenyl) -4,5-dihydroxy-cis-2,trans-4,cis-6-octatrienediamide 4' carboxy-4,5-dihydroxy-cis-2,trans-4,cis-6-octatrienedioanilic acid-gamma-lactone N butyl-4,5 -dihydroxy-2,4,6-octatrienedioamic acid-gam- The growth modifying and feed emciency promoting compositions of this invention are prepared by admixing in an amount suflicient to promote animal feed efficiency one or more of the compounds defined heretofore, with appropriate animal feed compositions. Such compositions can contain a variety of nutriments. and adjuvants. known and used in the art of animal husbandry in order to provide formulations adapted for ready and efiicient administration to various animals of the type recited hereinbefore. Thus, the feed efficiency promoting compositions can be prepared in the form of either powdered solids or liquids.

, Powdered or dust compositions of the invention are prepared by mixing one or more of the animal feed efficiency promoting compounds of this invention with finely. divided solids, preferably flours, such as wheat, corn, soya. bean and cotton-seed. Also, ground oyster shells; can be used, as well as finely divided attapulgite or bentonite These last mentioned substances also act as solid dispersing agents.

Where. one or more water immiscible oils, such as coco,- nut, olive, cotton-seed, and peanut oil, are used as a solvent for the active feed efficiency promoting agent, the water, oil and emulsifyingagent constitute an aqueous emulsion. carrier. Another technique is to dissolve the active feed efliciency promoting compound in an organic solvent, such as ethanol, acetone, or isopropylacetate, dis,- perse the resultant solution in a feed composition, and then'dry the feed' to remove the solvent.

Thus, the compositions of this invention can be used either in a liquid state or in a solid state. They can, for example, be. used in a concentrated form as part of an entire ration, as a powder, mash, pellet, capsule, tablet or other dry, semi-dry or liquid feed composition. The percentage by weight of the essential active feed eifi'ciency promoting ingredient will vary according to, the manner in whichthe particular composition is to be applied. but, in general; such percentage will be about 015% to 95% by weight of the feed efficiency promoting concentrate composition.

Both the solid and liquid feed efficiency promoting compositions can contain one or more surface-active agents in an amount sufiicient to render thecomposition readily dispersible in water. Such agents are, particularly. useful. if the compositions are to be, dispersed in,

. known as Tween80, which is a polyoxyethylene sorbitan mono-oleate with 20 moles of ethylene oxide for each mole of, sorbitan. Generally, the surface-active agent used will not comprisemore than. about-Sto 15% by, weight of a composition, and in. some compositions.

the percentage will be 1% or less.

The, amount. oftfeed, efficieney; promoting-active; ingrc: dient present in the compositions as,,fed;:to animals will q body weights.

vary with the type of animal involved, the feed efficiency promoting activity of the particular feed efficiency pro moting ingredient involved, the purpose for which the application is being made (i.e., short term or long term stimulation), the manner of application, and like variables. The optimum dosages required must be deter mined from a. consideration of all factors involved. Cer-. tain of the specific examples which follow will illustrate various kinds and amounts of application and the results obtained thereby. Oral administration or feeding of an effective dosage is the preferred method of use. In general, the exact amounts of the compounds usedin a feed composition depend upon the food consumption and eat ing habits of the animal concerned. particular for fowl and other domestic livestock, the preferred dosage is between about 0.001% and 1.0% by weight of the active feed efiiciency promoting compounds in the feedstutf, i.e., the feed composition. A particularly preferred range is 0.001% to 0.10%.. A particular concentration of active ingredient can be readily selected by persons skilled in the art in the light of the attendant circumstances and the nature of the effect desired in accordance with the teachings set forth herein.

If the feed efficiency promoting compositions are to be formulated without regard to the amount to be used in a feed composition for a specific animal, the compositions of the invention can be prepared in concentrated form suitable for dilution before administration.

Depending upon the eating habits and needs of the particular animal involved, the diets of an animal receiving the feed efficiency promoting composition of the present invention should be a normal, well-balanced one containing proper amounts of proteins, carbohydrates, fats, and mineral matter, supplemented with vitamins and antibiotics, as will be readily understood. Facts concerning the nutrition, feeding, care, and husbandry of the various classes of farm animals can be found in the book Feeds and Feeding by Frank B. Morrison, published by the Morrison Publishing Company of Ithaca, New York, 1948 (21st Ed.).

Where the feed efiiciency promoting compounds are to be placed in drinking water, good results are obtained at concentrations of the compounds comparable tothose employed when the compounds are substituents inafood composition.

-In order that the invention can be better understood,

the following examples are given in addition to the ex amples already set forth above. The examples illustrate" typical feedefiiciency promoting compositions of the invention, methods for their. preparation, feed efficiency promoting applicationsand the results obtained. Those skilled in the art-will appreciate that other. feed efficiency promoting compositions according to this inventioncan be prepared and applied in accordance with. theseexamples. ness of understanding only and. no unnecessary limitations are to be understood therefrom.

Examplev 1.A basal diet having a proteincontent.

calculated at 21% protein was prepared composed; of-

Thirtyweanling female rats were separated into thre'e"- groupsof ten rats eaclLon the basis of" litter mates and Group A bad a starting weight'of 5238 In general, and in,

Thus, the examples are herein givenv for. clear--.

grams, Group B 51.9 grams and Group C 51.2 grams. Over a period of five weeks, Group A was fedonly the above basal diet. Group B received the above basal diet admixed with 1 gram of 4,5-dihydroxy-cis-2,trans- 10 Example -5.-,4,5 dihydroxy-cis-2,trans-4, cis 6-dcta trienedioic acid, di-gamma-lactone/2,3-dimethylbutadiene 1:1 adduct. 1

Example 6.4,5 dihydroxy cis-2,trans-4,cis-6-octa Example 1, at a concentration of 0.10% by weight.

When administered to the diet of animals, outstanding improvement in feed efficiency and growth resulted:

Example 4.-2(and 3),6(and 7 )-dibutyl-4,5-dihydroxy- 4,cis-6-octatrienedioic acid, di-gamma-lactone, which can 5 trienedioic acid, di-gamma-lactone/1,6-hexanediamine 1:1 also be referred to as the transform oflA reaction product. i bifuran]-5,5-dione, per kilogram of the basal diet. The Example 7.-4, 5 dihydroxy cis-2,trans-4,cis-6-octa- 1 dilactone had been incorporated into the feed by metrienedioic =acid, di-gamma lactone/LS-dimethylpiperachanical mixing. Group C received the above basal diet zine 1:1 reaction product. admixed with 0.10 gram of the dilactone per kilogram 10 Example 8.2,2' --dihydroxy 2,2 bifuran 5,5- of feed. All three groups of rats were maintained in a (2H,2H)-dione. f temperature controlled environment in individual cages Example 9.--This example was carried out to demon for the entire five week period. Feed consumption and jst rate the outstanding feed etiicien'cy improvement due body weights were recorded once each week. At the to incorporation into animal feed of 4,5-dihydroxy-cisend of the five week test period, a marked improvement 2,trans-4,cis-fi-octatrienedioic acid, di-gamma-lactone at was noted in feed efficiency in the rats fed the dilactone, different protein concentrations in the diet of the animal. as can be seen from the following recorded data: Two diets were prepared: Diet A was identical to the basal diet described in Example land contained 21% GroupA GroupB Group 0 protein. The second diet, Diet B, had a protein content (Abiliage b Ki lated at 11% and was composed of the following animal) animal) animal) ingredients: i i Percent Gain grams 165 167 15s Corn gluten meal and essential amino acids 23.9 3 a 3 2? careless 0 ee ciene Cellufiour 22.8 Example 2.-Example 1 was repeated, except that five Crisco. 73 Cod hver 011 2.0 groups of rats were used, one receiving only the basal 1 i t n d 1 5 0 diet of Example 1 and the other four groups receiving i (con alplpg a l dz a "7-" the basal diet admixed with a feed efficiency promoting 0 amm mlx (contammg a ,reqmre v1 amms) compound according to this invention. The particular Six groups each containing eight female weanling rats feed efliciency promoting compounds used and their conwere each housed in individual cages, such that feed centration in the basal diet, together with the resultant consumption and body weight could be carefully obrecorded data, is as follows: i r served. Diet A was fed to Groups A, B and C, with the V Gain in Feed Feed Group Diet Weight Consumed Efiicieney (Average (Average (Average per-animal) per animal) per animal) Grams Grams am--- Basal diet only I 153 563 3.68 B. Basal diet with 0.01% by weight 4,5-dihydroxy-2(and 3), 161 .503 3.11 6(and 7)-dimethyl-cis-2, trans-4, cis-6-oetatrienedioic acid,

di-gamma4aetone. C. c-.- Basal diet with 0.01% by-weight 4-eh1ort 4-(p-chloroanilino)- 152 530 3. 49 i glydzroxy 2,4,6 oetatrienedioanilic acid gamma lactone ae. i p D Basil diet with 0.01% by weight 4,5-dihydroxy-cis2,eis-4, 145 509 3.52

eisdoetatrienedioic acid, di-gamma-lactone. E Basaldletwith0.01%-byweight4,5-dihydroxy-2,4,tl-oetatriene- 152 534 3.61

, dioic acid, til-sodium salt. V i t Exar nple 3.-Example 2 was repeated except that the Diet A fed to Group B containing 0.1% by weight of test was carried out over a four week period using three the di-gamma-lactone and the Diet A fed to Group C groups of rats, with the diets and results shown in the containing 0.01% of the di-gamma-lactone. Diet B was following table: fed to Groups D, E and F, with the diet B fed to Group Gainln Feed Feed Group Diet Weight Consumed Efliciency (Average (Average (Average per animal) per animal) per animal) Grams Grams A Basal diet only 138 477 3.45 B Basal diet with 0.1% by weight 4,5-dihydroxy-2(and 3), 6(and 137 468 3. 42

7)-diphenyl'cis-2, trans-4, cis-fipctatrienedioic acid, digamma laetone. C Basal diet with 0.01% by weight 4,5dihydroxy-2(and 3), 138 472 3.41

6(and 7)-di-2-naphthyl-cis-2, trans-4, cis-fi octatrienedioic I acid, di-gammaplactone.

i a Similar manner, the f l n feed efliciencx B containing 0.10% of the di-gamma-lactone and the motmg compounds were admixed with the basal diet of Diet B fed to Group F containing 0.01% by weight of the di-gammadactone. The rats were maintainedin an Standing improvement in feed efficiency was observed in cis-2,trans-4,cis-6-octatrienedioic acid, di-gamma-lactone. those animals whose diet contained the di-gammalactone,

1 1 particularly at the 6.10% level. The following data were recorded:

Example J0.This example was carried out to demonstrate the outstanding feed efiiciency improvement due to incorporation in a commercialswine feed animal diet (20% protien sow and pig feed) of 4,5'-dihydroxycis- 2 ,trans-4,cis-6-0ctatrienedioic acid, di-gamma-lacton'e.

Twenty female weanling rats were separated into two groups containing; ten rats each. Group A was fed a basal swine feed diet made from wheat flour middlings, corn meal, oats, alfalfa meal, soybean meal, meat scraps, animal fat, and supplemented with vitamins, minerals and antibiotics. v The animal fat was preserved with ;anti& oxidants. GroupB 'was fed the basal swine feed cliet containing, 0.1% by weight of the di-gamma-lactone. After a period of five weeks, the following were recorded! Feed 7 Gain in Feed Weight Consumed Efiiciency Group (Average (Average (Average per per per animal) animal) animal) Grams Grains A 140 7 512 4,09 B 1'42 533 3.75

Five Weeks Ten Weeks Diet Gainin Feed Gain ini Feed Weight Efinieney WVeight Efliciency (Average (Average- 7 (Average (Aver-age per per per per animal) animal) animal) animal) B'g. Kg; Basal only 39. 85 2; 32 O 2. 87 Basal with 0.1%

di-lactone 45. 00 2. 27 99. 60 2. 75

Example 12.--Two groups each containing 32' one da'y' old male chicks of crossed strain (Lancaster males X Nichols- #12 females) were fed a practical corn-soybean meal. basaldiet supplemented with vitamins and antibiotics. To one of the diets; 030l% by weight of 4,5- dihydroxy-cis-2,trans-4,cis-6-octatrienedioic acid, di-gamma-lactone was. added, while the other group: received no such additive The birds were maintainedv in wirellooid'eiectrically heated brooders. At the end" or four 12 weeks, the chicks were weighed and feed consumption data recorded. The following figures were obtained:

. Index of Gain in Feed Performance Weight Etficieney (Average gain Diet (Average (Average of weight per per per ammal/ animal) animal) Average feed efliciency per animal) v Grams. Grams Basal only 366 1.94 Basal with 0.01% dilactone 372 1. 86 200 Example HEY-Two groups of Holstein calves, three males per group, are compared for eight weeks as to their feed consumption and weight gain. Both groups are fed calf starter with occasional supplements of leafy hay. To the diet of one group is added 0.01% by weight of 4, 5 dihydroxy cis-2-trans-4,cis-6-octatrienedioic acid, digam1i1a-lactone. At the end of eight weeks, the calves receiving the growth stimulant according to this invention show a gain of 7% more weight and demonstrate a, marked improvement in feed efficiency on the basis of calf starter meal consumed per pound gained.

The above and similar examples can be'carried out in accordance with the teachings of this invention by substituting one or more other active feed efficiency promoting compounds within the scope of this invention for the feed efficiency promoting compounds recited in the above examples, and substituting other diets for the exemplarydiets recited above. Thus, the foregoing detailed description hasjbeen given forclearness of understanding only and no unnecessary limitations are to be understood therefrom.

The invention claimed is: V V

1. The method of promoting animal feed efiiciency which comprises incorporating in an animal feed at least one compound in an amount sutlicient to promote animal feed efficiency, said compound selected from the following groups:

(1) A compound represented by the formula:

wherein R and R are selected from the group consisting of hydrogen, monovalent hydrocarbon radicals free from non-aromatic unsaturation, haloalkyl, aralkyl, al-

koxyl, aryl, haloaryl, and alkoxyaryl; 0R wherein R is selected from the group consisting'of' hydroge'n, mono- I valent hydrocarbon radicals free from non a'r'oma-tic urisaturation, haloalkyl, aralkyl; alkoxyl, ar'yl', haloaryl, and alkoxyaryhprovided that only one'of the X and X radicals are GH in a single compound;-aiid OM wherein M is a cation; and" Y and' Y are selected from the group consisting of hydrogen and alkali metal;

(2) Monocycli rrionolactone' derivatives of com pounds of said formula wherein X and Y areremo'ved to form the corresponding monolactone;

('3') Mono'cyclic monolactone derivatives of compounds or said formula wherein X and Y are removed tororn uie corresponding monolactone; and

(4 .Dicyclic dila-ctone derivatives of compounds of said formula wherein X and Y and X and Y are removed to form the corresponding dilactone.

2. Animal feed composition comprising an animal feed and, in.an amount sufficient to promote animal feed eificiency, at least one compound selected from the fol lowing groups:

(1) A compound represented by the formula:

wherein R and R are selected from the group consisting of hydrogen, monovalent hydrocarbon radicals free from non-aromatic unsaturation, haloalkyl, arallcyl, al-

koxyl, aryl, haloaryl, and alkoxyaryl; 0R wherein R is selected from the group consisting of hydrogen, monovalent hydrocarbon radicals free from non-aromatic unsaturation, haloalkyl, aralkyl, alkoxyl, aryl, haloaryl, and alkoxyaryl, provided that only one of the X and X radicals are OH in a single compound; and OM Wherein M is a cation; and Y and Y are selected from the group consisting of hydrogen and alkali metal;

(2) Monocyclic monolactone derivatives of compounds of said formula wherein X and Y are removed to form the corresponding monolactone;

' (3) Monoeyclic monolactone derivatives of compounds of said formula wherein X and Y are removed to form the corresponding monolactone; and

(4) Dicyclic dilactone derivatives of compounds of said formula wherein X and Y and X and Y are removed to form the corresponding dilactone.

3. A feed efiiciency promoting composition comprising an animal feedstuif and a feed efiiciency promoting amount of 4,5-dihydroXy-cis-2,trans-4,cis-6-octatrienedioic acid, di-gamma-lactone.

No references cited. 

1. THE METHOD OF PROMOTING ANIMAL FEED EFFICIENCY WHICH COMPRISES INCORPORATING IN AN ANIMAL FEED AT LEAST ONE COMPOUND IN AN AMOUNT SUFFICIENT TO PROMOTE ANIMAL FEED EFFICIENCY, SAID COMPOUND SELECTED FROM THE FOLLOWING GROUPS: (1) A COMPOUND REPRESENTED BY THE FORMULA: 